So far, calcitonin, derived from eel, salmon, human beings, pigs, fowl, cattle, sheep, rats and stingray, has been known as natural calcitonin. Calcitonin peptides of such various origins are all polypeptides consisting of 32 amino acids that have the common characteristics, that is, the first and the seventh amino acids are L-cysteine, mercapto groups of these two amino acids form a disulfide bond and the carboxyl terminals are prolinamide.
The disulfide bond of these various calcitonins is expected to be unstable in a solution. To solve this problem, calcitonin derivatives were known to be prepared in which the first amino acid cysteine was deleted, the seventh amino acid cysteine was replaced by .alpha.-amino acid having a kind of lower carboxyalkylene group, and the side-chain carboxyl group of this amino acid and .alpha.-amino group of the second amino acid were combined to form an amide bond (Japanese Published Unexamined Patent Application Nos. 128993/76, 59688/78, and 112099/86). Particularly, the analogues based on the eel calcitonin sequence have been provided for practicable use as therapeutic agents against bone Paget disease, hypercalcemia, and osteoporosis. Analogues of this type in which single bonds in alkylene chain are partially replaced by double bond(s) or triple bond(s) are also known (WO 93/15106). As calcitonin analogues prepared for the same purpose, there are also known polypeptides in which the first amino acid is replaced by glycine or .beta.-alanine, the seventh amino acid is replaced by aspartic acid or glutamic acid, and an amide bond is formed between the .alpha.-amino group of the former and the side-chain carboxyl group of the latter, and peptides in which alkylene groups are partially replaced by phenylene group in addition to the above modifications (Japanese Published Unexamined Patent Application Nos. 262595/90 and 178993/91).
Further, many kinds of calcitonin analogues prepared for the purpose of improving physiological activities of natural calcitonin have been reported [e.g., Endocrinology, vol. 117, p. 801 (1985), Eur. J. Biochem., vol. 159, p. 125 (1986), Biochem. Biophys, Res. Commun., vol. 152, p. 203 (1988), Endocrinology, vol. 127, p. 163 (1990)].